Risk of serious adverse effects of biological and targeted drugs in patients with rheumatoid arthritis: a systematic review meta-analysis

DOI

Simon Tarp, Musculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, DenmarkDavid Geffen School of Medicine, University of California Los Angeles, CADivision of Rheumatology, University of Washington, Seattle, WA, USADivision of Rheumatology, University of Florence, Florence, ItalyDepartment of Epidemiology and BiostatisticsAmsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The NetherlandsDepartment of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USADepartment of Rheumatology, Aarhus University Hospital, Aarhus NDepartment of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, CopenhagenDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus NDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark., Daniel Eric Furst, Musculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, DenmarkDavid Geffen School of Medicine, University of California Los Angeles, CADivision of Rheumatology, University of Washington, Seattle, WA, USADivision of Rheumatology, University of Florence, Florence, ItalyDepartment of Epidemiology and BiostatisticsAmsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The NetherlandsDepartment of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USADepartment of Rheumatology, Aarhus University Hospital, Aarhus NDepartment of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, CopenhagenDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus NDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark., Maarten Boers, Musculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, DenmarkDavid Geffen School of Medicine, University of California Los Angeles, CADivision of Rheumatology, University of Washington, Seattle, WA, USADivision of Rheumatology, University of Florence, Florence, ItalyDepartment of Epidemiology and BiostatisticsAmsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The NetherlandsDepartment of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USADepartment of Rheumatology, Aarhus University Hospital, Aarhus NDepartment of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, CopenhagenDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus NDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.,

Henning Bliddal, Musculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, DenmarkDavid Geffen School of Medicine, University of California Los Angeles, CADivision of Rheumatology, University of Washington, Seattle, WA, USADivision of Rheumatology, University of Florence, Florence, ItalyDepartment of Epidemiology and BiostatisticsAmsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The NetherlandsDepartment of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USADepartment of Rheumatology, Aarhus University Hospital, Aarhus NDepartment of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, CopenhagenDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus NDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark., Ulrik Tarp, Musculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, DenmarkDavid Geffen School of Medicine, University of California Los Angeles, CADivision of Rheumatology, University of Washington, Seattle, WA, USADivision of Rheumatology, University of Florence, Florence, ItalyDepartment of Epidemiology and BiostatisticsAmsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The NetherlandsDepartment of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USADepartment of Rheumatology, Aarhus University Hospital, Aarhus NDepartment of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, CopenhagenDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus NDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark., Karsten Heller Asmussen, Musculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, DenmarkDavid Geffen School of Medicine, University of California Los Angeles, CADivision of Rheumatology, University of Washington, Seattle, WA, USADivision of Rheumatology, University of Florence, Florence, ItalyDepartment of Epidemiology and BiostatisticsAmsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The NetherlandsDepartment of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USADepartment of Rheumatology, Aarhus University Hospital, Aarhus NDepartment of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, CopenhagenDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus NDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.,

Anna Dossing, Musculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, DenmarkDavid Geffen School of Medicine, University of California Los Angeles, CADivision of Rheumatology, University of Washington, Seattle, WA, USADivision of Rheumatology, University of Florence, Florence, ItalyDepartment of Epidemiology and BiostatisticsAmsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The NetherlandsDepartment of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USADepartment of Rheumatology, Aarhus University Hospital, Aarhus NDepartment of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, CopenhagenDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus NDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark., Tanja Schjødt Jørgensen, Musculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, DenmarkDavid Geffen School of Medicine, University of California Los Angeles, CADivision of Rheumatology, University of Washington, Seattle, WA, USADivision of Rheumatology, University of Florence, Florence, ItalyDepartment of Epidemiology and BiostatisticsAmsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The NetherlandsDepartment of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USADepartment of Rheumatology, Aarhus University Hospital, Aarhus NDepartment of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, CopenhagenDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus NDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark., Steffen Thirstrup, Musculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, DenmarkDavid Geffen School of Medicine, University of California Los Angeles, CADivision of Rheumatology, University of Washington, Seattle, WA, USADivision of Rheumatology, University of Florence, Florence, ItalyDepartment of Epidemiology and BiostatisticsAmsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The NetherlandsDepartment of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USADepartment of Rheumatology, Aarhus University Hospital, Aarhus NDepartment of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, CopenhagenDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus NDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark., Robin Christensen, Musculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, DenmarkDavid Geffen School of Medicine, University of California Los Angeles, CADivision of Rheumatology, University of Washington, Seattle, WA, USADivision of Rheumatology, University of Florence, Florence, ItalyDepartment of Epidemiology and BiostatisticsAmsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The NetherlandsDepartment of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USADepartment of Rheumatology, Aarhus University Hospital, Aarhus NDepartment of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, CopenhagenDepartment of Clinical Biochemistry, Aarhus University Hospital, Aarhus NDepartment of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark Robin.Christensen@regionh.dk.

OBJECTIVES: To determine possible differences in serious adverse effects among the 10 currently approved biological and targeted synthetic DMARDs (b/ts-DMARDs) for RA.

METHODS: Systematic review in bibliographic databases, trial registries and websites of regulatory agencies identified randomized trials of approved b/ts-DMARDs for RA. Network meta-analyses using mixed-effects Poisson regression models were conducted to calculate rate ratios for serious adverse events (SAEs) and deaths between each of the 10 drugs and control (i.e. no b/ts-DMARD treatment), based on subjects experiencing an event in relation to person-years. Confidence in the estimates was assessed by applying the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE).